PURPOSEMyelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.METHODSA total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.RESULTSIPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.CONCLUSIONIPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.

Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes / Sauta, E.; Robin, M.; Bersanelli, M.; Travaglino, E.; Meggendorfer, M.; Zhao, L. -P.; Caballero Berrocal, J. C.; Sala, C.; Maggioni, G.; Bernardi, M.; Di Grazia, C.; Vago, L.; Rivoli, G.; Borin, L.; D'Amico, S.; Tentori, C. A.; Ubezio, M.; Campagna, A.; Russo, A.; Mannina, D.; Lanino, L.; Chiusolo, P.; Giaccone, L.; Voso, M. T.; Riva, M.; Oliva, E. N.; Zampini, M.; Riva, E.; Nibourel, O.; Bicchieri, M.; Bolli, N.; Rambaldi, A.; Passamonti, F.; Savevski, V.; Santoro, A.; Germing, U.; Kordasti, S.; Santini, V.; Diez-Campelo, M.; Sanz, G.; Sole, F.; Kern, W.; Platzbecker, U.; Ades, L.; Fenaux, P.; Haferlach, T.; Castellani, G.; Della Porta, M. G.. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 41:15(2023), pp. 2827-2842. [10.1200/JCO.22.01784]

Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes

Vago L.;Santoro A.;
2023-01-01

Abstract

PURPOSEMyelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.METHODSA total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.RESULTSIPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.CONCLUSIONIPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/152676
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